Exitotoxicity is an important cause of neuronal cell death in neurodegenerative diseases such as epilepsy. It is thought that excitotoxicity is initiated by overstimulation of glutamate receptors which causes an abnormal influx of Ca2+, thereby leading to neuronal cell damage. The GluR2 hypothesis states that certain neurological insults, such as kainate-induced status epilepticus, lead to downregulation of GluR2 gene expression and formation of Ca2+-permeable AMPA receptors. Regulation of these receptors is crucial in synaptic plasticity, neuronal development and diseases.
Earlier studies using hippocampal homogenate in Western blotting has shown decreased concentration of GluR2 due to epilepsy, but has however not determined where the change is. We believe that it takes place at the synaptic membrane. In this present investigation, I have examined the effects of chronic epilepsy on glutamate receptor subunit GluR2 in the stratum lucidum of the hippocampus subregion CA3 , using a rat model of mesial temporal lobe epilepsy.
6 rats received a shot of kainate which induced status epilepticus and thereafter recurrent spontaneous seizures. They were sacrificed 8 weeks later. The hippocampi was isolated and the CA3 subregion was sliced into 70-100 nm thick sections by an ultratome. For postembedding immunocytochemistry the sections were stained with antibodies against GluR2 coupled to colloid immunogold particles. A total of 180 electron microscopy pictures were taken and the immunogold particles were quantitated using analySIS. Statistical analysis was performed by SPSS.
The presynaptic active zone showed an increased concentration of GluR2 in the experiment group compared to the control group. The GluR2 concentration difference at the postsynaptic membrane and pre- and postsynaptic lateral membranes was insignificant.